The 2012 Gordon Research Conference (GRC) on Mutagenesis, titled A Delicate Balance: Cellular Mutation Pathways in Genetic Stability and Disease, will focus on the diverse mechanisms of mutagenesis and the manner in which they affect human health and disease. Mutagenesis provides the raw material for evolution, but elevated mutation rates and genetic instability are associated with aging and age-related diseases of cancer and neurodegeneration. Moreover, germline mutations confer inherited disease risk affecting many syndromes. Mutagenesis relates to the environment in that many environmental agents drive up mutation rates to increase disease risk in exposed individuals and potentiate inherited disease risk. Mutations in microbes provide important models for understanding basic mechanisms, and they are of importance in generating variants with increased antibiotic resistance or novel pathogenic features. The Program is distinguished by its focus on how mutations occur and give rise to the genetic and genomic instability manifest in cancer, neurodegeneration, premature aging and a host of inherited rare human diseases. Basic mechanisms of DNA maintenance are an integral part of this area and are also an important component of the program. The invited speakers represent the entire range of subjects cited above, and they cover a range laboratories of the academic, government and non-profit institute sectors. About 25% additional speakers will be selected from the submitted abstracts, which will ensure that the latest developments are included, and that beginning investigators are optimally represented on Program. The Program is organized into an opening keynote session, followed by daily morning and afternoon sessions on (1) Branching Pathways in Mutagenesis; (2) Oxidative Stress and Endogenous DNA Damage; (3) DNA Maintenance Pathways; (4) Recombinational Pathways, Good and Bad; (5) Problematic DNA Structures; (6) Hypermutation in the Microbial World; (7) Tissue-Specific and Aging-Related Mutagenesis; (8) Mutation and Disease. Abundant time is included for discussion within the sessions, with plentiful informal time outside the sessions for participants to interact. Daily poster sessions enable the presentation of work in progress and facilitate direct interaction among students, postdoctoral fellows, new investigators, and more senior figures in the field. Key objectives are to explore current knowledge at the frontier of mutagenesis research; to identify new research directions in mutagenesis; to identify therapeutic strategies to enhance genetic stability to offse disease, or to exploit mutagenesis itself as a therapy; to stimulate novel collaborations, especially exploiting work across systems and disciplines; and to enhance and promote the careers of young scientists and encourage their continuation in the field. The quality of the site (Salve Regina University, Newport, RI) will enhance these interactions while providing full access and support, and is itself a significant attraction for potential attendees. PUBLIC HEALTH RELEVANCE: Mutations, changes in DNA sequence that affect genetic function, are central to cancer formation, are associated with neurodegeneration and premature aging syndromes, and give rise to inherited disease risk. This meeting will explore the latest research developments in mechanisms that control genetic stability or give rise to mutations in a wide variety of systems. The program and venue will maximize dissemination of new results and enhance the interactions among a broad range of scientists doing research related to the field of mutagenesis.